This invention relates to a process for the isolation of ibuprofen from solids, and especially to a solvent extraction process for isolating ibuprofen from tablets.
Ibuprofen (2-[4'-isobutylphenyllpropionic acid) is a widely used analgesic, and is contained in a variety of over-the-counter medications. These are generally sold in tablet form; these tablets may have a variety of shapes and may be coated, e.g., sugar-coated, polymer film-coated, or the like. These tablets typically contain excipients, lubricants, binders, disintegrants, and/or fillers. The tablet compositions vary depending on the desired dosage, the tablet size, the chosen manufacturing method, and other factors. Examples of ibuprofen-containing tablets, well-known and commercially available in pharmacies throughout the United States and elsewhere, include ADVIL.RTM., COADVIL.RTM., MOTRIN.RTM. IB, and NUPRIN.RTM..
ADVIL.RTM. is a sugar-coated tablet comprising 200 mg ibuprofen, acacia, acetylated monoglycerides, carnauba wax or beeswax, calcium sulfate, colloidal silicon dioxide, dimethicone, iron oxide, lecithin, pharmaceutical glaze, povidone, sodium benzoate, sodium carboxymethylcellulose, starch, stearic acid, sucrose, and titanium dioxide.
COADVIL.RTM. is a sugar-coated tablet comprising 200 mg ibuprofen, 30 mg pseudoephedrine HCl, carnauba wax or equivalent wax, croscarmellose sodium, iron oxides, methylparaben, microcrystalline cellulose, propylparaben, silicon dioxide, sodium benzoate, sodium lauryl sulfate, starch, stearic acid, sucrose, and titanium dioxide.
MOTRIN.RTM. IB is a film-coated tablet comprising 200 mg ibuprofen, carnauba wax, cornstarch, hydroxypropyl methylcellulose, propylene glycol, silicon dioxide, pregelatinized starch, stearic acid, and titanium dioxide.
NUPRIN.RTM. is a film-coated tablet comprising 200 mg ibuprofen, carnauba wax, cornstarch, D&C Yellow No. 10, FD&C Yellow No. 6, hydroxypropyl methylcellulose, silicon dioxide, stearic acid, and titanium dioxide.
In the manufacture of such tablets, it is expected that a certain percentage of tablets will not meet all the manufacturing specifications, and cannot be sold or used. Unless the ibuprofen can be recycled, the ibuprofen in these off-spec tablets will be wasted, raising manufacturing and consumer costs and wasting natural resources. However, recycling is not economically feasible unless it can be done cheaply and produce ibuprofen pure enough to meet drug quality standards.
The recycling or recovery of ibuprofen from tablets is complicated by the presence of other ingredients, e.g. fillers and excipients, and by the use of tablet coatings. The ibuprofen must be well-separated from these substances to obtain the requisite drug purity. At the same time, it is desirable to obtain an ibuprofen yield that is as high as possible. If a film or other tablet coating is removed in a preisolation process, e.g., by physical abrasion, this additional step may increase costs and cause loss of tablet material, reducing yield.
A method for recovering ibuprofen and its salts by recrystallization and catalytic dehalogenation of the filtrate is disclosed in the Chemical Abstract 108:5688p of Japanese patent 62-185, 041 (1987) In this process, a crude solution in hexane is cooled to precipitate ibuprofen, and the filtrate is evaporated to obtain a chloride salt which is dissolved in 2% NAOH and heated over Pd catalysts to obtain ibuprofen.
A method for purifying ibuprofen is disclosed in the Chemical Abstract 109:73144d of Japanese patent 62-294,637 (1987). In this method, a mixture of crude ibuprofen and molecular sieves in hexane is refluxed, cooled, filtered, and cooled to 0.degree. C. to produce pure ibuprofen.
A method for determining ibuprofen in plasma by reversed-phase HPLC is disclosed in the Chemical Abstract 112:111406n of Chinese reference Sepu, 7(6), 357-8 (1989). In this method, ibuprofen is extracted from acidified plasma using a hexane-isopropanol (9:1) solvent and detected by HPLC.
A method for determining ibuprofen and its metabolites in human urine by HPLC is disclosed in Chai, et al., "Determination Of Ibuprofen And Its Major Metabolites In Human Urine By High-Performance Liquid Chromatography", J. Chromatography, 430, 93-101 (1988) . In this process, urine is acidified, extracted into hexane-propanol, and back-extracted into sodium bicarbonate, then neutralized and chromatographed. The extraction efficiencies were reported to be 94-100% for all compounds.